The project involves a new quantitative approach to analysis of strength of primary T cell reactions to major histocompatibility antigens of mouse and rat. The analysis will justify the claim that strength of such reactions is related to the number of specific T cells activated. The basis of this approach is the development of the Mixed Lymphocyte Interaction (MLI) as a titrateable potency assay. Selected histoincompatible rat and mouse allogeneic and xenogeneic combinations will be analyzed for reaction strength. Variations in reaction strength that are responder strain dependent will be subjected to genetic analysis to investigate the genetic basis for differences in strength of such reactions in terms of Ir gene like phenomena and antigen overlap. Xenogeneic rat-mouse MLI responses will also be used to clarify the concept of alloaggression in a similar analysis. An experimental approach in which T cells are selected for reactivity to a specific major histocompatibility haplotype and then tested for their potency in vitro as helpers in antibody responses to antigens the response to which is under the Ir-gene control will be used to answer the question, do conventional Ir-gene products control the specificity of reactions to transplantation antigens?